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Inhibitors of dihydroorotate dehydrogenase (DHODH) have been suggested for the treatment of rheumatoid arthritis, psoriasis, autoimmune diseases, Plasmodium, and bacterial and fungal infections. Here we present the structures of N-terminally truncated (residues Met30-Arg396) DHODH in complex with two inhibitors: a brequinar analogue (6) and a novel inhibitor (a fenamic acid derivative) (7), as wel
Objective The purpose of this study was to evaluate the effect of wet clothing removal or the addition of a vapor barrier in shivering subjects exposed to a cold environment with only limited insulation available. Methods Volunteer subjects (n = 8) wearing wet clothing were positioned on a spineboard in a climatic chamber (–18.5°C) and subjected to an initial 20 minutes of cooling followed by 3
Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function. Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a
Background: Osteocalcin (OC) is produced by osteoblasts during bone formation, and circulating OC has been used in clinical investigations as a marker of bone metabolism. OC is excreted into urine by glomerular filtration and can be found in urine as midmolecule fragments. Methods: We developed and evaluated three immunoassays (U-MidOC, U-LongOC, and U-TotalOC) for the detection of various molecul
BACKGROUND: There are few data on how patients on maintenance treatment of reflux oesophagitis take their medication. This study was designed to investigate the dosing patterns of patients on on-demand treatment and to compare lansoprazole with omeprazole in this regard. METHODS: Patients with reflux oesophagitis, initially treated until absence of symptoms, took capsules of either lansoprazole (3
With the increasing concerns about our environment and human health, more and more stringent emission limits have been specified. These adopted and still coming emission limits require and promote more accurate, less experiential methods to design and develop the combustors. In this thesis, computation fluid dynamics (CFD) technology, based on large eddy simulation (LES) and level set G-equation m
We have used the density functional B3LYP method to study the effect of hydrogen bonds from the histidine ligand in various haem proteins to carboxyl groups or to the carbonyl backbone. Hydrogen bonds to carbonyl groups (encountered in globins and cytochromes, for example) have a small influence on the geometry and properties of the haem site. However, hydrogen bonds to a carboxyl group (encounter
Objectives: To describe and compare the methods of pain management used by elderly individuals with chronic pain and requiring assistance with activities of daily living, depending on whether they live alone, with someone, at home or in special accommodations. Methods: This study comprised 294 people aged 76–100 years, identified as having chronic pain and requiring assistance with activities of
Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or
The electroweak production and subsequent decay of single top quarks in the t-channel is determined by the properties of the Wtb vertex, which can be described by the complex parameters of an effective Lagrangian. An analysis of a triple-differential decay rate in t-channel production is used to simultaneously determine five generalised helicity fractions and phases, as well as the polarisation of
Dietary fibre and whole grains are recommended to prevent the development of type 2 diabetes. Low glycaemic index foods that are rich in fibre are recommended to control blood glucose levels. Gastric emptying, together with other factors, regulate the postprandial blood glucose response. A delay in the gastric emptying rate (GER) leads to a lower postprandial blood glucose concentration. However,
Nuclear power has significantly improved performance over the last thirty years. This improvement has been based on a philosophy of control. That is, for each issue that must be managed to achieve safe performance, a pre-determined barrier must be established. In addition to the barriers that were designed into the plant, a large range of programs, processes and procedures have been developed to d
BACKGROUND: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound. OBJECTIVE: To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometriu
Populärvetenskaplig sammanfattning: Drunkningsrisk för skogen? Att mängden vatten i marken är viktig för att granen ska kunna ha så god tillväxt som möjligt är ingen nyhet. Är det för fuktigt drunknar rötterna, på grund av att de inte får en tillräckligt mycket syre. I denna studie har två markberedningsmetoder, högläggning och ingen markberedning, jämförts för att se vilket alternativ som är mestNorway spruce is a coniferous tree with many different fields of application. For an example, they are used as Christmas trees, decoration and as timber or pulpwood. The reason why many foresters in Sweden tend to choose spruce as their main species for plantation is partly because of their fast growth rate and partly because the main products are derived from the actual tree trunks. In the forest
This paper describes a study examining four different GARCH models AR(1)-GARCH(1,1), AR(1)-EGARCH(1,1), AR(1)-APGARCH(1,1) and AR(1)-GJR-GARCH(1,1), and their ability to predict future volatility and thereby providing more reliable estimates for Value-at-Risk. The study is based on daily observations for the return of the OMX Stockholm 30 Index, during the time period 31st December 1996 to 29th De
By comparing the work-hours-related experiences of women in two countries that differ in their labor protections and their social-service provision—in other words, that differ in the extent to which neoliberalism holds sway—this manuscript sheds light on the implications of neoliberalism in terms of women’s working conditions.Specifically, we analyze the protections offered by each country that co
Purpose: Hodgkin lymphoma (HL) survivors are known to have increased cardiac mortality and morbidity. The risk of developing cardiovascular disease after involved node radiotherapy (INRT) is currently unresolved, inasmuch as present clinical data are derived from patients treated with the outdated mantle field (MF) technique. Methods and Materials: We included all adolescents and young adults with
BACKGROUND: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-te
Until now, computationally designed enzymes exhibited low catalytic rates1, 2, 3, 4–5 and required intensive experimental optimization to reach activity levels observed in comparable natural enzymes5, 6, 7, 8–9. These results exposed limitations in design methodology and suggested critical gaps in our understanding of the fundamentals of biocatalysis10,11. We present a fully computational workflow
Importance: Emerging evidence suggests that cholesterol plays a role in breast cancer (BC) metabolism, raising the possibility that cholesterol-lowering medications, such as statins, may improve BC prognosis. Objective: To evaluate the association between postdiagnosis statin initiation and BC mortality using an emulated target trial approach. Design, Setting, and Participants: This observational
